Benzofused heterozryl amide derivatives of thienopyridines useful as therapeutic agents, pharmaceutical compositions including the same, and methods for their use

A pharmaceutical composition for the treatment of a hyperproliferative disorder in a mammal comprising a therapeutically effective amount of a compound represented by the formula I:

• wherein:
• Y is —NH—, —O—, —S—, or —CH2—;
• Z is —O— or —N—;
• R14 is a C1-C6 alkyl, C1-C6 alkylamino, C1-C6 alkylhydroxy, C3-C10 cycloalkyl, C1-C6 alkyl C3-C10 cycloalkyl or methylureido group;
• R15 and R17 are independently H, halo, or a C1-C6 alkyl group unsubstituted or substituted by one or more R5 groups;
• R16 is H or a C1-C6 alkyl group when Z is N, and R16 is absent when Z is —O—;
• R11 is H, C1-C6 alkyl, C3-C10 cycloalkyl, —C(O)NR12R13, —C(O)(C6-C10 aryl), —(CH2)t(C6-C10 aryl), —(CH2)t(5 to 10 membered heterocyclic), —(CH2)tNR12R13, —SO2NR12R13 or —CO2R12, wherein said C1-C6 alkyl, —C(O)(C6-C10 aryl), —(CH2)t(C6-C10 aryl), and —(CH2)t(5 to 10 membered heterocyclic) moieties of the said R11 groups are unsubstituted or substituted by one or more R5 groups;
• each R5 is independently selected from halo, cyano, nitro, trifluoromethoxy, trifluoromethyl, azido, —C(O)R8, —C(O)OR8, —OC(O)R8, —OC(O)OR8, —NR6C(O)R7, —C(O)NR6R7, —NR6R7, —OR9, —SO2NR6R7, C1-C6 alkyl, C6-C10 cycloalkyl, C1-C6 alkylamino, —(CH2)jO(CH2)qNR6R7, —(C H2)tO(CH2)qOR9, —(CH2)tOR9, —S(O)j(C1-C6 alkyl), —(CH2)t(C8-C10 aryl), —(CH2)t(5 to 10 membered heterocyclic), —C(O)(CH2)t(C6-C10 aryl), —(CH2)tO(CH2)j(C6-C10 aryl), —(CH2)tO(CH2)q(5 to 10 membered heterocyclic), —C(O)(CH2)t(5 to 10 membered heterocyclic), —(CH2)jNR7(CH2)qNR6R7, —(CH2)jNR7CH2C(O)NR6R7, (CH2)jNR7(CH2)qNR9C(O)R8, (CH2)jNR7(CH2)tO(CH2)qOR9, —(CH2)jNR7(CH2)qS(O)j(C1-C6 alkyl), —(CH2)jNR7(CH2)tR6, —SO2(CH2)t(C6-C10 aryl), and —SO2(CH2)t(5 to 10 membered heterocyclic), the —(CH2)q— and —(CH2)t— moieties of the said R5 groups optionally include a carbon-carbon double or triple bond, and the alkyl, aryl and heterocyclic moieties of the said R5 groups are unsubstituted or substituted with one or more substituents independently selected from halo, cyano, nitro, trifluoromethyl, azido, —OH, —C(O)R8, —C(O)OR8, —OC(O)R8, —OC(O)OR8, —NR6C(O)R7, —C(O)NR6R7, —(CH2)tNR6R7, C1-C6 alkyl, C3-C10 cycloalkyl, —(CH2)t(C6-C10 aryl), —(CH2)t(5 to 10 membered heterocyclic), —(CH2)tO(CH2)qOR9, and —(CH2)tOR9;
• each R6 and R7 is independently selected from H, OH, C1-C6 alkyl, C3-C10 cycloalkyl, —(CH2)t(C6-C10 aryl), —(CH2)t(5 to 10 membered heterocyclic), —(CH2)tO(CH2)qOR9, —(CH2)tCN(CH2)tOR9, —(CH2)tCN(CH2)tR9 and —(CH2)tOR9, and the alkyl, aryl and heterocyclic moieties of the said R6 and R7 groups are unsubstituted or substituted with one or more substituents independently selected from hydroxy, halo, cyano, nitro, trifluoromethyl, azido, —C(O)R8, —C(O)OR8, —CO(O)R8, —OC(O)OR8, —NR9C(O)R10, —C(O)NR9R10, —NR9R10, C1-C6 alkyl, —(CH2)t(C6-C10 aryl), —(CH2)t(5 to 10 membered heterocyclic), —(CH2)tO(CH2)qOR9, and —(CH2)tOR9, where when R6 and R are both attached to the same nitrogen, then R and R7 are not both bonded to the nitrogen directly through an oxygen;
• each R8 is independently selected from H, C1-C10 alkyl, C3-C10 cycloalkyl, —(CH2)t(C6-C10 aryl), and —(CH2)t(5 to 10 membered heterocyclic);
• t is an integer from 0 to 6;
• j is an integer from 0 to 2;
• q is an integer from 2 to 6;
• each R9 and R10 is independently selected from H, —OR6, C1-C6 alkyl, and C3-C10 cycloalkyl;
• and
• each R12 and R13 is independently selected from H, C1-C6 alkyl, C3-C10 cycloalkyl, —(CH2)t(C3-C10 cycloalkyl), —(CH2)t(C6-C10 aryl), —(CH2)t(5 to 10 membered heterocyclic), —(CH2)tO(CH2)qOR9, and —(CH2)tOR9, and the alkyl, aryl and heterocyclic moieties of the said R12 and R13 groups are unsubstituted or substituted with one or more substituents independently selected from R5, or R12 and R13 are taken together with the nitrogen to which they are attached to form a C5-C9 azabicyclic, aziridinyl, azetidinyl, pyrrolidinyl, piperidyl, piperazinyl, morpholinyl, thiomorpholinyl, isoquinolinyl, or dihydroisoquinolinyl ring, wherein said C5-C9 azabicyclic, aziridinyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, isoquinolinyl, or dihydroisoquinolinyl rings are unsubstituted or substituted with one or more R substituents, where R12 and R13 are not both bonded to the nitrogen directly through an oxygen;
• or a pharmaceutically acceptable salt or solvate thereof and a pharmaceutically acceptable carrier.